Next-generation sequencing (NGS) is increasingly used in transplantation settings, but also as a method of choice for in-depth analysis of population-specific HLA genetic architecture and its linkage ...to various diseases. With respect to complex ethnic admixture characteristic for East Croatian population, we aimed to investigate class-I (HLA-A, -B, -C) and class-II (HLA-DRB1, -DQA1, -DQB1) HLA diversity at the highest, 4-field resolution level in 120 healthy, unrelated, blood donor volunteers. Genomic DNA was extracted and HLA genotypes of class I and DQA1 genes were defined in full-length, -DQB1 from intron 1 to 3' UTR, and -DRB1 from intron 1 to intron 4 (Illumina MiSeq platform, Omixon Twin algorithms, IMGT/HLA release 3.30.0_5). Linkage disequilibrium statistics, Hardy-Weinberg departures, and haplotype frequencies were inferred by exact tests and iterative Expectation-Maximization algorithm using PyPop 0.7.0 and Arlequin v3.5.2.2 software. Our data provide first description of 4-field allele and haplotype frequencies in Croatian population, revealing 192 class-I and class-II alleles and extended haplotypic combinations not apparent from the existing 2-field HLA reports from Croatia. This established reference database complements current knowledge of HLA diversity and should prove useful in future population studies, transplantation settings, and disease-associated HLA screening.
Dietary supplementation with compounds that possess antioxidant and anti-inflammatory properties (
polyunsaturated fatty acids (PUFAs), selenium, vitamin E, lutein), has been shown to positively ...correlate with improvements in chronic conditions, although understanding of these combined effects in healthy humans is limited. The study aimed to evaluate the effects of enriched eggs consumption on oxidative status and inflammatory conditions in healthy volunteers. We hypothesized that a three-week diet containing enriched eggs can alter the immune response of healthy adults towards anti-inflammatory conditions.
34 participants consumed 3 hard-boiled hen eggs per day (21 days): Control group-regular hen eggs (
-3 PUFAs = 438 mg, selenium = 0.054 mg, lutein = 0.330 mg and vitamin E = 1.785 mg) (
= 14); 4Nutri group-hen eggs enriched with 4 nutrients (
PUFAs = 1026 mg, selenium = 0.06 mg, lutein = 1.85 mg and vitamin E = 3.29 mg) (
= 20). Samples were taken before and after the protocol. Serum concentrations of lipid mediators and cytokines were measured with enzyme-linked immunosorbent assay (ELISA) and antibody-based, magnetic bead reagent kits on the Luminex platform, respectively. Serum oxidative stress and antioxidant capacity were measured using standardized methods, while gene expression in peripheral blood mononuclear cells (PBMCs) was measured via real-time PCR.
Decreased serum levels of pro-inflammatory interleukin 17A (IL-17A) and an increased neuronal nitric oxide synthase (nNOS) expression in the 4Nutri group, together with alteration of metabolites produced via cyclooxygenase (COX) pathways in the Control group, suggest a shift towards anti-inflammatory conditions in participants who consumed enriched hen eggs.
Present results suggest that the combined action of
PUFAs and antioxidants may have a protective role in resting, non-inflammatory conditions.
NCT04564690.
Tramadol is a commonly used analgesic in intensive care units (ICUs) for acute postoperative pain. Conversion of tramadol into active metabolites may be impaired in inflammatory states. ...Catechol-O-methyltransferase may influence pain. The aim of the study was to examine differences in the analgesic effect of tramadol between ICU patients with and without signs of systemic inflammation. Forty-three patients were admitted to ICU after a major abdominal surgery. The patients received a dose of 100 mg of tramadol intravenously every 6 hours during the first 24 hours after surgical procedure. Pain scores were measured by the Numeric Rating Scale before and 30 minutes after tramadol administration in awake patients. Systemic inflammation was considered when at least two of the following postoperative parameters were present in the first 24 hours of ICU admission: fever or hypothermia, tachycardia, pCO.sub.2 <4.3 kPa, white blood cells >12000/mm (3) or <4000/mm.sup.3, or preoperative value of C-reactive protein (CRP) >50 mg/L or/and procalcitonin (PCT) >0.5 mg/L. Catechol-O-methyltransferase was analyzed postoperatively. Fifteen (34.8%) patients met the criteria for systemic inflammation. Tramadol was proven to be an effective analgesic for the treatment of postoperative pain regardless of the presence of systemic inflammation (p<0.05). Lower perception of pain before tramadol application was observed in patients with systemic inflammation, but the difference was not significant. A negative correlation was observed between the preoperative values of CRP and PCT and the analgesic effect of tramadol assessed at the second measurement point (r=-0.3S8, p=0.03, and r=-0.364, p=0.02, respectively). Catechol-O-methyltransferase variants were not in correlation with pain and opioid consumption. Based on our findings, tramadol is effective in lowering pain scores after major abdominal surgery irrespective of the presence of systemic inflammation. Key words: Analgesia; Critical care; Systemic inflammatory response; Catechol-O-methyltransferase; Tramadol
This study aimed to investigate the effect of 7-day high-salt (HS) and the specific role of oxidative stress on vascular low-grade inflammation initiation in young salt-resistant healthy individuals. ...30 young healthy individuals adhered to a 7-day low-salt (LS) diet (3.5 g salt/day), followed by a 7-day high-salt (HS) diet (~14.7 g salt/day) protocol. Pro- and anti-inflammatory cytokines, frequencies of peripheral blood Th17 and Treg cells, Th17/Treg ratio, enzymes SGK1, and p38/MAP kinase, as well as biomarkers of endothelial activation and oxidative stress, were measured before and after the 7-day HS diet protocol. Short-term HS diet significantly increased serum level of pro-inflammatory cytokines INF-γ, TNF-α, IL-9, and IL-17A levels, but also of anti-inflammatory cytokines IL-10 and TGF-β1. Relative amount of total SGK1 significantly increased, following the 7-day HS diet. Increased oxidative stress level, following HS diet, was negatively associated with the frequency of Treg cells. The increase in relative amount of total SGK1 in peripheral mononuclear cells following 7-day HS diet suggests lymphocyte (re)activation, in response to HS intake, resulting in enhanced production of pro-inflammatory (IL-17, INF-γ), but also anti-inflammatory cytokines (IL-10 and TGF-β1). Increased oxidative stress, due to HS loading, alters immune regulatory mechanisms, presumably via effects on Treg cells.
Lipidni profil kod žena u postmenopauzi Marušić, Romana; Ormanac, Klara; Marczi, Saška ...
Medica Jadertina (Zagreb),
08/2023, Letnik:
53, Številka:
2
Journal Article
Recenzirano
Objectives: The main objectives of the research are to examine the incidence of hyperlipoproteinemia in postmenopausal women and to determine the differences in lipid profile considering age, ...duration of menopause and body mass index in postmenopausal women. Respondents and methods: The research is structured as cross-sectional with historical data. The research used data collected during regular check-ups in primary health care clinics in Osijek Health Center from November 2021 to March 2022. Collected data: demographic data, information on the duration of menopause, body mass, body height, body mass index, values of total, LDL, HDL cholesterol and triglycerides, and data on associated diseases. Results: 98 postmenopausal women were included in the research, of which over 50% had elevated total and LDL cholesterol values, and 39.8% had elevated triglyceride values. Subjects aged 45 to 65 years and subjects with a duration of menopause of 10 or more years had significantly higher values of total and LDL cholesterol while no difference was observed in the lipid profile with regard to the body mass index. Using the SCORE2 table, it was estimated that 65% of the subjects had a very high cardiovascular risk, and only 6% of the subjects achieved the target values of LDL cholesterol in accordance with the cardiovascular risk. Conclusion: There is a very high incidence of hyperlipoproteinemia in postmenopausal women, and the age and duration of menopause have an impact on the poorer achievement of the target values of the lipid profile, while the body mass index showed no impact. Given the high prevalence of subjects with a very high cardiovascular risk (SCORE 2 tables), intensive interventions are needed at all levels of health care, especially at the primary level of health care, which include non-pharmacological and pharmacological methods of treating hyperlipoproteinemia.
Cilj istraživanja: Osnovni ciljevi istraživanja jesu ispitati incidenciju hiperlipoproteinemije u žena upostmenopauzi i utvrditi razlike u sastavnicama lipidnog profila obzirom na dob, trajanje menopauze iindeks tjelesne mase.Ispitanici i metode: Istraživanje je ustrojeno kao presječno s povijesnim podacima. Za istraživanje suse koristili podaci prikupljeni u ambulantama primarne zdravstvene zaštite u Domu zdravlja Osijek, odstudenoga 2021. do ožujka 2022. g. a prikupljeni su na redovitim kontrolama. Prikupljeni podaci:demografski podaci, podaci o trajanju menopauze, tjelesna masa, tjelesna visina, indeks tjelesne mase,vrijednosti ukupnog, LDL, HDL kolesterola i triglicerida, te podaci o pridruženim bolestima.Rezultati: U istraživanje je uključeno 98 ispitanica od kojih preko 50 % njih ima povišene vrijednostiukupnog i LDL kolesterola, a 39,8 % povišene vrijednosti triglicerida. Ispitanice starosti 45 do 65 godina iispitanice s trajanjem menopauze od 10 ili više godina imaju značajno više vrijednosti ukupnog i LDLkolesterola, dok nije uočena razlika u lipidnom profilu obzirom na indeks tjelesne mase. UpotrebomSCORE2 tablice procijenjeno je da 65 % ispitanica ima vrlo visok kardiovaskularni rizik, a samo 6 %ispitanica postiglo je ciljne vrijednosti LDL kolesterola u skladu s kardiovaskularnim rizikom.Zaključak: Incidencija hiperlipoproteinemije u postmenopauzalnih žena je vrlo visoka, a starija dob idulje trajanje menopauze povezani su sa slabijim postizanjem ciljnih vrijednosti lipidnog profila, dokindeks tjelesne mase nije pokazao utjecaj. Obzirom na visoku zastupljenost ispitanica s vrlo visokimkardiovaskularnim rizikom (SCORE 2 tablice), potrebne su intenzivne intervencije na svim razinamazdravstvene zaštite, posebice primarnoj razini zdravstvene zaštite, a koje uključuju i nefarmakološke ifarmakološke metode liječenja hiperlipoproteinemija.
Most studies examining tramadol metabolism have been carried out in non-surgical patients and with oral tramadol. The aim of this study was 1) to measure concentrations of tramadol,
-demethyltramadol ...(ODT), and
-demethyltramadol (NDT) in the surgical patients admitted to the intensive care unit (ICU) within the first 24 postoperative hours after intravenous application of tramadol, and 2) to examine the effect of systemic inflammation on tramadol metabolism and postoperative pain.
A prospective observational study was carried out in the surgical ICU in the tertiary hospital. In the group of 47 subsequent patients undergoing major abdominal surgery, pre-operative blood samples were taken for
polymorphism analysis. Systemic inflammation was assessed based on laboratory and clinical indicators. All patients received 100 mg of tramadol intravenously every 6 h during the first postoperative day. Postoperative pain was assessed before and 30 min after tramadol injections. Tramadol, ODT, and NDT concentrations were determined by high-performance liquid chromatography.
analysis revealed 2 poor (PM), 22 intermediate (IM), 22 extensive (EM), and 1 ultrafast metabolizer. After a dose of 100 mg of tramadol, t
of 4.8 (3.2-7.6) h was observed. There were no differences in tramadol concentration among metabolic phenotypes. The area under the concentration-time curve at the first dose interval (AUC
) of tramadol was 1,200 (917.9-1944.4) μg ×h ×L
. NDT concentrations in UM were below the limit of quantification until the second dose of tramadol was administrated, while PM had higher NDT concentrations compared to EM and IM. ODT concentrations were higher in EM, compared to IM and PM. ODT AUC
was 229.6 (137.7-326.2) μg ×h ×L
and 95.5 (49.1-204.3) μg ×h ×L
in EM and IM, respectively (
= 0.004). Preoperative cholinesterase activity (ChE) of ≤4244 U L
was a cut-off value for a prediction of systemic inflammation in an early postoperative period. NDT AUC
were significantly higher in patients with low ChE compared with normal ChE patients (
= 0.006). Pain measurements have confirmed that sufficient pain control was achieved in all patients after the second tramadol dose, except in the PM.
polymorphism is a major factor in
-demethylation, while systemic inflammation accompanied by low ChE has an important role in the
-demethylation of tramadol in postoperative patients. Concentrations of tramadol, ODT, and NDT are lower in surgical patients than previously reported in non-surgical patients. Clinical Trial Registration: ClinicalTrials.gov, NCT04004481.
Ovarian hyperstimulation syndrome (OHSS) is a rare, yet severe, iatrogenic complication of ovulation induction therapy during assisted reproductive procedures. Our group previously detected atypical ...cells in the ascitic fluid of OHSS patients, although no malignancy developed during follow up. Here, the aim was to perform a comparative analysis of the cytokines present in the abdominal fluid of patients affected by OHSS versus patients with advanced ovarian cancer, a benign adnexal mass, or ovarian endometriosis.
This prospective, non-randomized study was conducted at the Clinical Center of the University of Pecs Department of Obstetrics and Gynecology/Reproductive Center between October 2016 and March 2018. Abdominal fluid samples were obtained from 76 patients and subjected to Luminex analysis. The samples were collected from patients with OHSS (OHSS; n = 16), advanced ovarian cancer (OC; n = 22), a benign adnexal mass (BAM; n = 21), or ovarian endometriosis (EM; n = 17). Data were subjected to the non-parametric Kruskal-Wallis test and Spearman's rank correlation coefficient to identify statistical differences between the four study groups.
Leukocytosis and hemoconcentration were detected in the peripheral blood of OHSS patients. Abdominal fluid analysis further revealed significantly higher levels of interleukin (IL)-6, IL-8, IL-10, and transforming growth factor (TGF)-β in both the OHSS and OC groups compared to the BAM and EM groups. The highest concentration of vascular endothelial growth factor (VEGF) was detected in the OC group, while a significantly lower level was detected in the OHSS group. Moreover, VEGF levels in OC and OHSS groups were significantly elevated compared to the levels in the BAM and EM groups.
Vasoactive and hematogenic cytokines were present at higher levels in both the OHSS and OC abdominal fluid samples compared to the fluid samples obtained from the peritoneal cavity of the BAM patients. It is possible that these cytokines play an important role in the formation of ascites.
An introduction of the permanent positive charge by methylation of heterocyclic nitrogen on a series of previously studied bis-urea phenanthridine derivatives substantially changed their interactions ...with DNA and RNA as well as biological activity. At variance to non-methylated analogues, novel methylated derivatives interacted with DNA/RNA not only at pH 5 but also at pH 7, and some compounds switched the DNA binding mode from the minor groove binding (non-methylated derivatives) to the intercalation (novel, methylated derivatives). Moreover, selective ds-RNA over ds-DNA thermal stabilization of previously observed non-methylated derivatives was reversed for novel, methylated derivatives. The variation of a linker length connecting two urea–phenanthridinium conjugates regulated their binding modes toward double stranded polynucleotides. All novel compounds were able to distinguish between polynucleotides of A–T(U) and G–C basepair composition by a specific fluorescence change. Moreover, the introduction of the permanent positive charge on the phenanthridinium moiety resulted in significantly higher biological potency in respect to non-methylated analogues.
A methylation of heterocyclic nitrogen on a previously studied bis-urea phenanthridines substantially changed their interactions with DNA, RNA and biological activity. Novel compounds act as basepair selective fluorescence probes.
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A series of new peptides (8-25) containing different unnatural amino acids of the adamantane type (1-6), was synthesized. Possible cytotoxic activity on human cervical adenocarcinoma (HeLa), larynx ...carcinoma (HEp-2), colon carcinomas (HT-29, Caco-2), poorly differentiated cells from lymph node metastasis of colon carcinoma (SW-620), mammary gland adenocarcinoma (MCF-7), and melanoma (HBL) cells were tested by the MTT assay. The results were compared with the effect of methionine-enkephalin (Tyr-Gly-Gly-Phe-Met, or opioid growth factor, OGF), and its shorter N-terminal fragments. Peptide analogues containing C(alpha alpha)-dialkylated glycine (Aaa1, 1) or C(alpha)-alkylated glycine (Aaa2, 2) amino acid residues showed antitumor activity against melanoma, larynx carcinoma, colon carcinomas, and colon metastasis cell lines in vitro. The pentapeptide Tyr-(R,S)-Aaa2-Gly-Phe-Met (18) was the most effective analogue especially against the most antitumor drug-resistant cell lines HEp-2 and SW-620. Apoptosis as a mode of cell death was confirmed in these tumor cells after exposure to pentapeptide 18.
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